The generation and identification of specific agents for the diagnosis, prevention, and treatment of human diseases requires access to vast collections of useful chemistries. With the advent and rapid development of a variety of techniques for the creation and screening of antibody libraries, monoclonal antibodies against disease targets have become one of the major categories of new drug candidates. Since for human use, in addition to specificity and efficacy, safety is of primary concern, libraries of human monoclonal antibodies have become of particular importance.
At present, the development of human antibody-based drug candidates are typically identified by screening of human antibody libraries comprising a random collection of antibody sequences from human repertoires that are typically unrelated to their intended application or applications. Each antibody library created from a specific human donor potentially contains antibodies to every component, physiology, and metabolic alteration stemming from, or creating, every unique challenge that the donor has encountered, challenged, and surmounted over the course of that individual's lifetime. As typical human antibody libraries made with the current approaches are constructed without the knowledge of the health history of donors, little is known of what would be expected in the resulting immunoglobulin repertoires.
Thus, it is of great interest to create antibody libraries from individuals who have successfully survived or are surviving an encounter with specific diseases because their resulting repertoires include antibodies that were used by the donor to defend specifically against a relevant disease. It is also important to provide methods for the efficient screening and handling of such libraries, including the ability to remove or isolate negative or positive elements, eliminate undesirable content, and produce human antibodies with improved properties.
The present invention addresses these needs by providing methods and means for the creation, screening and handling of donor-specific antibody libraries from individuals who have been exposed to and survived or are surviving an encounter with a specific target disease.